Molecular complexes that direct rhodopsin transport to primary cilia

Department of Surgery, Division of Ophthalmology, University of New Mexico, Albuquerque, NM 87131, USA.
Progress in Retinal and Eye Research (Impact Factor: 8.73). 10/2013; 38. DOI: 10.1016/j.preteyeres.2013.08.004
Source: PubMed


Rhodopsin is a key molecular constituent of photoreceptor cells, yet understanding of how it regulates photoreceptor membrane trafficking and biogenesis of light-sensing organelles, the rod outer segments (ROS) is only beginning to emerge. Recently identified sequence of well-orchestrated molecular interactions of rhodopsin with the functional networks of Arf and Rab GTPases at multiple stages of intracellular targeting fits well into the complex framework of the biogenesis and maintenance of primary cilia, of which the ROS is one example. This review will discuss the latest progress in dissecting the molecular complexes that coordinate rhodopsin incorporation into ciliary-targeted carriers with the recruitment and activation of membrane tethering complexes and regulators of fusion with the periciliary plasma membrane. In addition to revealing the fundamental principals of ciliary membrane renewal, recent advances also provide molecular insight into the ways by which disruptions of the exquisitely orchestrated interactions lead to cilia dysfunction and result in human retinal dystrophies and syndromic diseases that affect multiple organs, including the eyes.

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    • "FIP3 binding, which causes an activating change in ASAP1 (Inoue et al., 2008), also exposes its Rabin8 binding site, so we conclude that Rabin8 binds to the catalytically active ASAP1 in complex with Rab11a and FIP3. Rabin8 preference for the active conformation of ASAP1 might prevent its premature inclusion into the ciliary targeting complex, as Rabin8 is necessary for the later post-Arf4 stage of RTC budding (Wang and Deretic, 2014). Rabin8-mediated activation of Rab8 renders RTCs competent for fusion with the periciliary plasma membrane, because activated Rab8 regulates the final stages of polarized membrane traffic, fusion of ciliary-targeted carriers and ciliogenesis (Deretic et al., 1995; Knodler et al., 2010; Moritz et al., 2001; Nachury et al., 2007; Wang et al., 2012; Yoshimura et al., 2007). "
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